Medical leads

ABSTRACT

Medical leads, such as medical electrical leads and medical neurological leads, that include a polymeric material that includes a silicone-urethane-containing polymer having improved hydrolytic stability.

CROSS-CITE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationNo. 61/619,078, filed on Apr. 2, 2012, U.S. Provisional Application No.61/725,361, filed on Nov. 12, 2012, and U.S. Provisional Application No.61/725,364, filed on Nov. 12, 2012, all of which are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

Silicone-urethane polymers (i.e., silicone-polyurethanes orpolydimethylsiloxane-polyurethanes) are a class of materials that wasdeveloped to fill the need for soft biostable materials needed inimplantable medical devices. Such materials are commercially availablefrom sources such as Aortech (e.g., under the tradename Elast-Eon E2A)and DSM (e.g., under the tradename PurSil 35). The entire industrybelieved that this was the answer to the need for oxidatively stablematerials. It was generally believed that because silicone-polyurethanesas a class of materials were considered primarily polyurethane, thisimproved oxidative stability was sufficient for many uses.

SUMMARY OF THE INVENTION

The present invention is directed to the discovery that degradation of aclass of silicone-urethane polymeric materials developed for use inimplantable medical devices occurs hydrolytically, even though it wasthought such materials were oxidatively stabilized. Such discovery hasled to the development of new materials that have improved hydrolyticstability. Thus, the present disclosure provides a medical lead with apolymeric material that has improved hydrolytic stability.

In one embodiment, the present disclosure provides a medical lead thatincludes an elongated lead body including a polymeric material, whereinthe polymeric material includes a silicone-urethane polymer havinghydrolytic stability greater than that of a Reference Polymer X, aReference Polymer Y, or both Reference Polymers X and Y. The medicallead can be in the form of a medical electrical or neurological lead.

In one embodiment, the present disclosure provides a medical electricallead, including: an elongated lead body having a first lumen, extendinglongitudinally along said lead body; and a conductor (e.g., coiledconductor) located within and extending longitudinally along said lumen;wherein the lead body includes a polymeric material (particularlyinsulation material), wherein the polymeric material includes asilicone-urethane polymer having hydrolytic stability greater than thatof a Reference Polymer X, a Reference Polymer Y, or both ReferencePolymers X and Y.

In one embodiment, the present disclosure provides a medical,neurological lead for use in electrical signaling and/or drug delivery.The lead includes: an elongated body with a distal portion, a centralportion and a proximal portion; wherein the body includes delivery meansextending to said distal portion; and wherein the lead body includes apolymeric material (particularly insulation material), wherein thepolymeric material includes a silicone-urethane polymer havinghydrolytic stability greater than that of a Reference Polymer X, aReference Polymer Y, or both Reference Polymers X and Y.

In certain embodiments, the delivery means includes electrical signaldelivery means. Preferably, the electrical signal delivery means is animplantable lead having at least one electrode. In certain embodiments,the delivery means includes drug delivery means. Preferably, the drugdelivery means includes a catheter.

Herein, “Reference Polymer X” is a silicone-urethane polymer (i.e.,silicone-polyurethane) with a soft and hard segment weight ratio of60/40, respectively, with the soft segment containing 80 wt-% PDMS(molecular weight approximately 1000 Da, n=10-11 repeat units) and 20wt-% PTMO (molecular weight approximately 1000 Da) and the hard segmentcomprised of BDO (1,4-butanediol) and MDI (4,4′-methylene diphenyldiisocyanate). Reference Polymer X is available commercially as PurSil35 from DSM Biomedical.

Herein, “Reference Polymer Y” is a silicone-urethane polymer (i.e.,silicone-polyurethane) with a soft and hard segment weight ratio of60/40, respectively, with the soft segment containing 80 wt-% PDMS(molecular weight approximately 1000 Da, n=10-11 repeat units) and 20wt-% PHMO (molecular weight approximately 700 Da) and the hard segmentcomprised of BDO (1,4-butanediol) and MDI (4,4′-methylene diphenyldiisocyanate). Reference Polymer Y is available commercially asElast-Eon E2A from Aortech Int.

In certain embodiments, the silicone-urethane polymer can be preparedfrom one or more polydialkyl-, polydiaryl-, or polyalkylaryl-siloxanemonomers other than a polydimethylsiloxane monomer.

In certain embodiments, the silicone-urethane polymer can be preparedfrom a mixture of one or more polydimethylsiloxane monomers and at leastone other monomer selected from polydialkyl-, polydiaryl-, andpolyalkylaryl-siloxane monomers other than a polydimethylsiloxanemonomer.

In certain embodiments, the silicone-urethane polymer can be preparedfrom a polydimethylsiloxane diol monomer with a number average molecularweight equal to or higher (preferably higher) than 1000 Da. In certainembodiments, the silicone-urethane polymer can be prepared from apolydimethylsiloxane diol monomer with a number average molecular weightequal to or higher than 1500 Da. In certain embodiments, thesilicone-urethane polymer can be prepared from a polydimethyl siloxanediol monomer with a number average molecular weight equal to or higherthan 2000 Da.

In certain embodiments, the silicone-urethane polymer can be preparedfrom a polydimethyl siloxane diol monomer of the formula:

wherein n is from 10 to 1500 and m is from 0 to 18 (preferably n is from15 to 150 and m is from 5 to 18, and more preferably n is from 20 to 150and m is 10 to 18).

In certain embodiments, the silicone-urethane polymer can be preparedfrom a PDMS (polydimethyl siloxane) diol with hydrophobic endgroups/blocks. In certain embodiments, the PDMS diol with hydrophobicend groups can be prepared from a hydride-terminated siloxane and anunsaturated alcohol selected from the group of 9-decen-1-ol,10-undecen-1-ol, oleyl alcohol, and combinations thereof.

In certain embodiments, the silicone-urethane polymer can be preparedfrom a hydrophobic co-soft segment and/or chain extender.

In certain embodiments, the silicone-urethane polymer is crosslinked.

The terms “comprises” and variations thereof do not have a limitingmeaning where these terms appear in the description and claims.

The words “preferred” and “preferably” refer to embodiments of thedisclosure that may afford certain benefits, under certaincircumstances. However, other embodiments may also be preferred, underthe same or other circumstances. Furthermore, the recitation of one ormore preferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the disclosure.

In this application, terms such as “a,” “an,” and “the” are not intendedto refer to only a singular entity, but include the general class ofwhich a specific example may be used for illustration. The terms “a,”“an,” and “the” are used interchangeably with the term “at least one.”The phrases “at least one of” and “comprises at least one of” followedby a list refers to any one of the items in the list and any combinationof two or more items in the list.

As used herein, the term “or” is generally employed in its usual senseincluding “and/or” unless the content clearly dictates otherwise. Theterm “and/or” means one or all of the listed elements or a combinationof any two or more of the listed elements.

Also herein, all numbers are assumed to be modified by the term “about”and preferably by the term “exactly.” As used herein in connection witha measured quantity, the term “about” refers to that variation in themeasured quantity as would be expected by the skilled artisan making themeasurement and exercising a level of care commensurate with theobjective of the measurement and the precision of the measuringequipment used.

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range as well as the endpoints (e.g., 1to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

When a group is present more than once in a formula described herein,each group is “independently” selected, whether specifically stated ornot. For example, when more than one R group is present in a formula,each R group is independently selected.

The above summary of the present disclosure is not intended to describeeach disclosed embodiment or every implementation of the presentdisclosure. The description that follows more particularly exemplifiesillustrative embodiments. In several places throughout the application,guidance is provided through lists of examples, which examples can beused in various combinations. In each instance, the recited list servesonly as a representative group and should not be interpreted as anexclusive list.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings where like numerals refer to like components throughoutseveral views:

FIG. 1 is a diagram of a lead which incorporates a preferred embodimentof the present disclosure.

FIG. 2 is a cross-sectional view of the lead body of the lead shown inFIG. 1.

FIG. 3 is a cross-section of an exemplary lead body.

FIG. 4 is a diagram of a neurological electrical lead which incorporatesa preferred embodiment of the present disclosure.

FIG. 5 is a diagram of a neurological drug delivery lead whichincorporates a preferred embodiment of the present disclosure.

FIG. 6 is a 37° C. master curve showing the hydrolysis kinetics of asilicone polyurethane ‘Polymer X.’

FIG. 7 is a proton NMR spectrum of the model compound control (top) andthe model compound after 8 weeks at 60° C. (bottom).

FIG. 8 is an ²⁹Si NMR spectra of the model compound after 9 weeks at 60°C. (top spectrum) compared to the time zero model compound (bottomspectrum). A new peak at −14.2 ppm appeared in the hydrolyzed sample dueto the formation of Si—OH.

FIG. 9 is a 37° C. master curve showing the hydrolysis kinetics of twosilicone polyurethane polymers made with different PDMS chain lengths(n=2 and n=10 PDMS repeat units respectively). The silicone polyurethanewith PDMS chain length n=10-11 is the same composition as shown in FIG.6 (‘Polymer X’), whereas the silicone polyurethane with chain length n=2does not contain PTMO and similarly contains BDO and MDI.

FIG. 10 is a graph of the percent new PDMS peak versus time for anether-containing model compound and a hexamethylene model compound.

FIG. 11 is a plot of the first order hydrolysis rates for twopolyurethane-PDMS model compounds.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

It has been previously believed that polymer degradation in animplantable medical device occurs predominately by oxidation. Mechanismsfor stabilizing polymers against oxidative degradation have beenincorporated into such polymers; however, it has been discovered thathydrolytic degradation still occurs. Thus, the present inventionprovides a medical lead (e.g., electrical or neurological lead) with apolymeric material that has improved hydrolytic stability.

Medical leads are used to transmit electrical signals to and frommedical devices such as pacemakers and neurostimulators, for example.The lead body is usually made from a piece of polymeric tubing having around cross-section exterior and a round cross-section lumen. Typicallya coiled metallic electrical conductor having a round cross-section isplaced in the lumen completely filling it. The tubing protects andinsulates the conductor. The coiled conductor can usually receive astylet to help position and place the lead during implantation. Thereare many examples of medical electrical leads, including, for example,those described in U.S. Pat. Nos. 6,785,576, 5,303,704, 5,999,858,6,149,678, 4,947,866, 5,922,014, 5,628,778, 4,497,326, 5,443,492,7,860,580, and 5,303,704.

As an exemplary embodiment of a medical electrical lead, FIG. 1 is adiagram of a lead assembly 10, which incorporates a preferred embodimentof the invention. The lead body 26 carries four electrodes includingventricular electrodes 12 and 13 and atrial electrodes 14 and 15. Withinthe lead body are four conductors, one coupled to each of the electrodesand extending proximally to a corresponding electrical connector. Theproximal end of the lead assembly 10 has a dual in-line connectorassembly including connector pin 16, coupled to electrode 12, connectorring 18, coupled to electrode 13, connector pin 20, coupled to electrode14 and connector ring 22, coupled to electrode 15. A stylet 24 may beinserted into the lead through pin 16 to stiffen it as an aid toimplantation.

Lead body 26 in FIG. 1 is preferably fabricated of silicone rubber,polyurethane or other implantable polymer. In particular, lead body 26is preferably fabricated of a polymer of the present disclosure.

Electrodes 12, 13, 14, and 15 in FIG. 1 are preferably fabricated ofplatinum alloy or other biocompatible metal. Connectors 16, 18, 20, and22 are preferably fabricated of stainless steel or other biocompatiblemetal.

As illustrated the lead includes electrodes which may serve as means fordelivery of stimulation pulses and as means for sensing physiologicalelectrical signals. It should also be understood that a lead accordingto the present invention may also include means for sensing otherphysiological parameters, such as pressure, oxygen saturation,temperature, or pH. The lead may include electrodes only, otherphysiologic sensors only, or a combination of both.

FIG. 2 is a cross-section through the lead body 26. In this view, it canbe seen that lead body 26 is provided with four pie-shaped or generallytriangular lumens. The first lumen 44 contains a first coiled conductor43. The second lumen 46 contains a second coiled conductor 45. The thirdlumen 48 contains a third coiled conductor 47. The fourth lumen 50contains a fourth coiled conductor 49. The conductors 43, 45, 47, and 49are preferably fabricated of MP35N alloy or other biocompatible metal.In the drawing each coiled conductor is shown as a multi-filar coil.However monofilar coils are useful as well. One of the four conductorsis coupled to pin 16 and also serves to receive a stylet.

The lead body may employ the multi-lumen configuration illustrated overits entire length, with two of the lumens unused distal to electrodes 14and 15. Alternatively, a transition to a lead body having a coaxial orside by side two-lumen configuration as typically used in bipolar pacingleads may occur at or distal to electrodes 14 and 15. As seen in crosssection, the representative fourth lumen 50 has three walls each havinga radius of curvature substantially greater than the radius of curvatureof the conductor coil.

These walls include two substantially planar walls 51 and 52 eachextending along a radius of the body and an outer curved wall 53,extending along the outer circumference of the lead body. The walls arejoined to one another along corners 55, 57, and 58 each of which have aradius of curvature substantially less than the radius of curvature ofthe conductor coils, as seen in this cross-section.

In certain embodiments, contact between a coil of a conductor and theinner surface of a lumen will be limited to those portions of the innersurfaces of the lumen which have a substantially greater radius ofcurvature than the conductor coil. Contact will thus be limited todiscrete points of contact, rather than along substantial lengths of theindividual coils, as would occur in prior leads employing circular coilsand circular lumens of similar sizes. Contact will occur only alongwalls 51, 52 and 53, and not in corners 55, 57 and 59. Along the lengthof the lead, individual coils will contact various points on all threewalls 51, 52, and 53.

The present medical electrical lead includes a polymeric material of thepresent disclosure as part or all of lead body 26, but theoreticallythis could apply to any insulator on the lead body.

FIG. 3 is a cross-section of another exemplary lead body showing severalinsulation layers: a primary insulation layer 1, which encapsulates theconductors; a secondary insulation layer 2, which contains the lumensfor the conductors; and a tertiary outer insulation layer 3. Thesilicone polyurethane polymer of this disclosure forms part or all ofany of these insulation layers.

Medical, neurological leads are used for insertion into the human body,for transmission of therapeutic drugs and/or electrical signals to bodyorgans such as the spinal cord or brain, for acute and chronic painrelief, acute and chronic treatment of disease, and the like. The leadsare used in programmable, electronic, implantable devices which deliverdrugs and/or electrical stimulation in programs of therapy for thebenefit of mankind.

Implantable electrical devices are capable of relieving chronic,inoperable pain by interfering with the transmission of pain signals inthe spinal cord and brain. Implantable drug delivery devices are capableof delivering pain relieving drugs to the same dramatic effect. Bothtypes of devices are also capable of new therapies for treatment of avariety of diseases. An advantage of the electrical devices is thattypically no drugs are necessary. With the drug delivery devices, anadvantage is that drug dosages are reduced relative to other therapiesbecause the drugs are delivered directly to desired locations oftherapy, rather than in remote locations such as the blood vessels ofthe extremities, and without concern for bodily elimination or chemicalinteraction.

With the electrical devices, electrical stimulation is typicallydelivered from the devices to the body through wired leads, toelectrodes. The electrodes are located on and exposed to the body on thedistal extremity of the leads, and the leads typically extend into andalong the epidural space of the spinal cord, or into the brain atsurgically drilled boreholes. The leads may also be subcutaneous wherenecessary. As an example, leads may extend from devices implanted abovethe clavicles, under the skin, to a bore hole atop the skull, and thencedeep into brain tissue.

With the drug delivery devices, catheters, which for purposes of thisdescription are also considered “neurological leads,” extend in similarways. Leads in the described applications are typically smooth walled,plastic, tubular members, although variation is possible.

There are many examples of medical neurological leads, including, forexample, those described in U.S. Pat. Nos. 5,058,584, 5,865,843, U.S.Pat. Pub. No. 2008/0275429. Medical neurological leads include, forexample, paddle leads such as disclosed in U.S. Pat. No. 8,166,880,in-line cylindrical leads such as disclosed in U.S. Pat. No. 7,184,838,and drug delivery catheters such as disclosed in U.S. Pat. Pub. No.2012/0245533. These leads/catheters can be placed in numerous locations.Electrode leads are used in the epidural space, within the brain itself,in the sacral root, and within blood vessels. Cuff type electrodes, asin U.S. Pat. No. 5,282,468, can be mounted around nerve bundles orfibers. Drug delivery catheters can be placed in/adjacent the spinalcolumn or any location within the vascular system.

The polymeric material of the present disclosure may be used as all orpart of the lead body, as insulation, as an inner or outer layer, etc.

Referring to FIGS. 4 and 5, an exemplary lead of the disclosure includesa distal portion 10, and associated central and proximal portions notshown. As known to persons of ordinary skill in the art, if electrical,the lead may connect to an electrical signal generating device(hereafter “a signal generator”) which may or may not be implantable inwhole or in part into the human body. If the lead is a drug deliverylead, the lead may connect to a drug pump, which also may or may not beimplantable. In either case, the lead is intended to have at least aportion engaged in the tissue of the body. Depending on the application,the lead may engage tissue in the proximal, central, or distal portionsof the lead. The lead may or may not enter the epidural space whichsurrounds the spinal cord, or the lead may enter the brain through theskull. Generally, the lead is substantially elongated, with thedimension of its length one hundred or more times the dimension of itswidth.

Again if electrical, as in FIG. 4, the lead 410 may include one or moreelectrodes, such as an electrode designated 412. The electrode may beannular, surrounding the lead body, or in other shape or form. If a drugdelivery lead, as in FIG. 5, the lead 522 may include one or moreopenings for transmission of drugs from the drug pump to the body, inthe place of electrodes, or in addition to electrodes.

The lead 410 or 522 is desirably, generally circular in cross-section,although variations are within contemplation. Focusing on an electricallead of FIG. 4, for illustration, an insulating, annular, external leadsheath or body 414 surrounds an electrically transmissive internal core416, shown in phantom. The core 416 frequently takes the form of ahelically wound or coiled wire, interconnected to the distalelectrode(s) and the proximal signal generator. The wire has a directionof its winding, which is right hand or left hand, clockwise orcounterclockwise. As desired, although not presently contemplated, thelead may also include additional intermediate or other layers, or othercomponents.

FIG. 4. shows an electrical lead having a helical groove 418, andassociated helical land 420. FIG. 5 shows a drug deliver lead orcatheter having a liquid insulating, annular, external lead sheath orbody 524 surrounds a liquid transmissive internal and open core orpassage 526, shown in phantom.

Polymers of the present disclosure are elastomers. An “elastomer” is apolymer that is capable of being stretched to approximately twice itsoriginal length and retracting to approximately its original length uponrelease. Polymers of the present disclosure can be made of two or moredifferent monomers. They can be random, alternating, block, star-block,segmented copolymers, or combinations thereof. Preferably, the polymersare segmented copolymers (i.e., containing a multiplicity of both hardand soft domains or segments on any polymer chain) and are comprisedsubstantially of alternating relatively soft segments and relativelyhard segments.

As used herein, a “hard” segment is one that is crystalline at usetemperature, or amorphous with a glass transition temperature above usetemperature, or when in the water saturated state at body temperature, ahard segment has a Tg of about 30° C. (below body temperature, but abovethat of the soft segments −100° C. to −30° C.), and a “soft” segment isone that is amorphous with a glass transition temperature below usetemperature (i.e., rubbery). A crystalline or glassy moiety or hardsegment is one that adds considerable strength and higher modulus to thepolymer. Similarly, a rubbery moiety or soft segment is one that addsflexibility and lower modulus, but may add strength particularly if itundergoes strain crystallization, for example. The random or alternatingsoft and hard segments are linked by urethane groups and the polymersmay be terminated by hydroxyl, amine, and/or isocyanate groups orsurface modified end groups.

Certain of the segments, either the hard or the soft segments, or both,can include a silicone-containing moiety. The presence of thesilicone-containing moiety provides a polymer that is typically moreresistant to oxidation because it displaces some of the oxidativelysusceptible ether soft segments if a polymer with comparable hardness istargeted but still has a relatively low glass transition temperature(Tg). Furthermore, preferably, both the hard and soft segments arethemselves substantially ether-free, ester-free, and carbonate-freepolyurethanes. The silicone-containing groups (i.e., moieties) are ofthe formula —O—Si(R)₂—, and are typically provided bypolydimethylsiloxane (PDMS). Although the use of silicone-containinggroups in a polymer provides improved oxidative stability when used inan implantable medical device, this is not sufficient for hydrolyticstability.

Typically, polyurethanes are made by a process in which a diisocyanateis reacted with diol to form a prepolymer. The resulting prepolymer canbe further reacted with a chain extender, such as a diol. To make apolysiloxane-polyurethane, the diol will typically include thepolysiloxane moiety.

The present disclosure provides various mechanisms for improvinghydrolytic stability of a silicone-polyurethane.

One approach is the use of PDMS diol monomers with number averagemolecular weights equal to or higher (preferably higher) than 1000 Da(most of the commercially available silicone urethanes include PDMSsegments of 1000 daltons). In certain embodiments, the silicone-urethanepolymer can be prepared from a polydimethyl siloxane diol monomer with anumber average molecular weight equal to or higher than 1500 Da. Incertain embodiments, the silicone-urethane polymer can be prepared froma polydimethyl siloxane diol monomer with a number average molecularweight equal to or higher than 2000 Da.

In some embodiments, suitable PDMS monomers are of the formula:

wherein 10<n<1500.

In some embodiments, suitable PDMS monomers are of the formula:

wherein n is from 10 to 1500 and m is from 0 to 18 (preferably n is from15 to 1500, or 15 to 150, and m is from 5 to 18, and even morepreferably n is from 20 to 1500, or 20 to 150, and m is 10 to 18).

Such longer PDMS chains can contribute to the modification of themorphological phases of the polymer. For example, introduction of a newlinkage between the urethane and the silicone moiety can provide ahydrophobic protective barrier to the silicone.

Another approach to slow down the hydrolysis of the siloxane bond in asilicone-polyurethane is the use of various alkyl- or aryl-siloxanemonomers other than PDMS. Although many documents discuss the use ofsuch monomers, they are not typically incorporated into any experimentalor commercial materials. Generally, such monomers can be demonstrated bythe following oligomeric or polymeric structure:

wherein, each R is independently a divalent aliphatic group, each X isindependently an hydroxyl or amine group, each R₁ and R₂ areindependently a C1-C4 alkyl group, phenyl, or a combination thereof, nis from 1 to 1500, with the proviso that not all R₁ and R₂ groups aremethyl.

Examples of some polysiloxane homopolymers include those such aspolydiethylsiloxane, polypropylsiloxane, polydibutylsiloxane, etc., andcopolymers of these species. These polysiloxane contain bulky sidegroups and could provide the steric hindrance to retard or stop thehydrolysis reaction. Some structures, and methods of making them, aredescribed below in the Examples Section.

Another approach to slow down the hydrolysis of silicone-polyurethane isto increase the overall hydrophobicity of the polyurethane. This can bedone by introducing hydrophobic moieties into urethane at the PDMS chainend. For example, a PDMS diol with hydrophobic end groups can beprepared from a hydride-terminated polysiloxane and an unsaturatedalcohol such as: 9-decen-1-ol, 10-undecen-1-ol, or oleyl alcohol.

Another way to increase the hydrophobicity of polyurethane is to use ahydrophobic co-soft segment and/or chain extender. Examples of somediols that can be used as the co-soft segment/chain extender to preparepolyurethanes are described in the Examples Section.

The silicone hydrolysis reaction may be facilitated or catalyzed byneighboring functional groups that could coordinate (hydrogen bond,dipole-dipole, etc.) and stabilize intermediate hydrolysis productsduring the hydrolysis reaction. For example, the PDMS species employedin commercially available silicone polyurethane formulations containsether functionality in the PDMS chain end groups. Further neighboringurethane groups which are polar and could hydrogen bond could alsocoordinate to siloxane ether bonds and participate in facilitating thehydrolysis reaction. The proximity of the neighboring urethane group tothe siloxane bonds could be important. By utilizing PDMS diols withoutcoordinating groups (ether, etc.) and/or by reducing the proximity ofthe siloxane ether to urethane groups, for example, by introducing alkylend groups with increased chain length, silicone polyurethanes withimproved hydrolytic stability could result.

Yet another method to slow down the hydrolysis of silicone-polyurethaneis to crosslink the silicone domain(s) in the polymer. Crosslinkedmaterials are mechanically stable due to their networked structure. Forexample, silicone adhesive/sealant is mechanically stable for a longperiod time even in contact with water. In an analogous manner to thisphenomenon, silicone-polyurethane with crosslinked polysiloxane moietyshould have longer mechanical stability than that without crosslinking.

In contrast to a previous crosslinking method for making siliconepolyurethane (US 2007/0027285 A1), which formed the crosslinkedpolyurethane during synthesis of polyurethane polymer, the crosslinkingreaction of the present disclosure focuses on crosslinking thepolyurethane after synthesis of the polyurethane polymer. Preferably,the crosslinking reaction of the PDMS soft segment is typicallyinitiated at the extrusion process step and is completed in a post-cureprocess.

One approach to crosslink PDMS is to use a radical reaction, similar tothe crosslinking method used in the silicone tubing. Since thepolyurethane tubing is extruded at high temperature, a radical generatorsuch as dicumyl peroxide, di-t-amyl peroxide, and di-t-butyl peroxidewill be used to crosslink the PDMS domain in the polyurethane. Duringthe extrusion, a small percentage of the peroxide is introduced into thepolyurethane and mixed in the extruder. These peroxides decompose athigh temperature and have reasonable half-lives at 150-160° C. Thisallows the PDMS domain to be crosslinked while the polyurethane is beingextruded. Post-extrusion cure is also possible. Alternatively, avinylmethylsiloxane-dimethylsiloxane copolymer or other structures canbe introduced to facilitate the crosslinking. Another approach tocrosslink the PDMS in the urethane is to prepare thesilicone-polyurethane with polysiloxane copolymer containingcrosslinkable units that will only react with each other at hightemperature. For example, a copolymer of PDMS with multiple pendentbenzocyclobutene (BCB) groups is used as a soft segment for makingpolyurethane. The crosslinked PDMS domain will maintain the mechanicalproperties longer than the non-crosslinked version upon the same degreeof degradation (mainly hydrolysis). Additionally, the hydrophobic BCBgroup will decrease the water absorption in the polyurethane, which inturn slows down the hydrolysis reaction. By controlling the content ofBCB in the polysiloxane oligomer, the crosslinking density can becontrolled. This is discussed in greater detail in the Examples Section.

Illustrative Embodiments

-   1. A medical lead comprising an elongated lead body comprising a    polymeric material, wherein the polymeric material comprises a    silicone-urethane polymer having hydrolytic stability greater than    that of a Reference Polymer X, a Reference Polymer Y, or both    Reference Polymers X and Y.-   2. The medical lead of embodiment 1 in the form of a medical    electrical or neurological lead.-   3. A medical electrical lead comprising:

an elongated lead body having a first lumen, extending longitudinallyalong said lead body; and

a conductor located within and extending longitudinally along saidlumen;

wherein the lead body comprises a polymeric material, wherein thepolymeric material comprises a silicone-urethane polymer havinghydrolytic stability greater than that of a Reference Polymer X, aReference Polymer Y, or both Reference Polymers X and Y.

-   4. A medical, neurological lead for use in electrical signaling    and/or drug delivery comprising:

an elongated body with a distal portion, a central portion and aproximal portion;

wherein the body includes delivery means extending to said distalportion; and

wherein the elongated body comprises a polymeric material, wherein thepolymeric material comprises a silicone-urethane polymer havinghydrolytic stability greater than that of a Reference Polymer X, aReference Polymer Y, or both Reference Polymers X and Y.

-   5. The lead of embodiment 4 wherein the delivery means comprises    electrical signal delivery means.-   6. The lead of embodiment 5 wherein the electrical signal delivery    means is an implantable lead having at least one electrode.-   7. The lead of embodiment 4 wherein the delivery means comprises    drug delivery means.-   8. The lead of embodiment 7 wherein the drug delivery means    comprises a catheter.-   9. The lead of any of embodiments 1 through 8 wherein the polymeric    material is polymeric insulation material.-   10. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from one or more polydialkyl-,    polydiaryl-, or polyalkylaryl-siloxane monomers other than a    polydimethylsiloxane monomer.-   11. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a mixture of one or more    polydimethylsiloxane monomers and at least one other monomer    selected from polydialkyl-, polydiaryl-, and polyalkylaryl-siloxane    monomers other than a polydimethylsiloxane monomer.-   12. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a polydimethyl siloxane    diol monomer with a number average molecular weight equal to or    higher than 1000 Da.-   13. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a polydimethyl siloxane    diol monomer of the formula:

wherein n is from 10 to 1500 and m is from 0 to 18.

-   14. The lead of embodiment 13 wherein n is from 15 to 1500 and m is    from 5 to 18.-   15. The lead of embodiment 14 wherein n is from 20 to 1500 and m is    10 to 18.-   16. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a polydimethyl siloxane    diol monomer of the formula:

wherein n is from 10 to 1500.

-   17. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a PDMS diol with    hydrophobic end groups/blocks.-   18. The lead of embodiment 17 wherein the PDMS diol with hydrophobic    end groups are prepared from a hydride-terminated siloxane and an    unsaturated alcohol selected from the group of 9-decen-1-ol,    10-undecen-1-ol, oleyl alcohol, and combinations thereof.-   19. The lead of any of embodiments 1 through 9 wherein the    silicone-urethane polymer is prepared from a hydrophobic co-soft    segment and/or chain extender.-   20. The lead of any of embodiments 1 through 19 wherein the    silicone-urethane polymer is crosslinked.-   21. The lead of any of embodiments 1 through 20 as dependent on    embodiment 3 wherein the conductor is a coiled conductor.

EXAMPLES Reference Polymer X

Reference Polymer X is a silicone polyurethane with a soft and hardsegment weight ratio of 60/40, respectively, with the soft segmentcontaining 80 wt-% PDMS (molecular weight approximately 1000 Da, n=10-11repeat units) and 20 wt-% PTMO (poly(tetramethylene oxide), molecularweight approximately 1000 Da) and the hard segment comprised of BDO(1,4-butanediol) and MDI (4,4′-methylene diphenyl diisocyanate).

Reference Polymer Y

Reference Polymer Y is a silicone polyurethane with a soft and hardsegment weight ratio of 60/40, respectively, with the soft segmentcontaining 80 wt-% PDMS (molecular weight approximately 1000 Da, n=10-11repeat units) and 20 wt-% PHMO (poly(hexamethylene oxide), molecularweight approximately 700 Da) and the hard segment comprised of BDO(1,4-butanediol) and MDI (4,4′-methylene diphenyl diisocyanate).

Method of Evaluating Hydrolytic Stability

Hydrolytic stability of various polymers is determined by monitoring themolecular weight changes of the polymer upon exposure to water anddetermining the kinetics of the hydrolysis reaction. The number averagemolecular weight (Mn) is directly related to the concentration ofpolymer species chain ends and consequently is a useful parameter fordetermining reaction kinetics (rates of reactions). For chemicaldegradation processes that result in chain scission, for examplehydrolysis, the parameter 1/Mn is directly proportional to theconcentration of chain ends, which increase as the chain scissionreaction proceeds. The hydrolysis rate is typically constant as theconcentrations of susceptible bonds and absorbed water are relativelyconstant until the late stages of hydrolysis, where the polymertypically exhibits significant water uptake and possibly dissolution,consequently a plot of 1/Mn with time would give a straight line withthe slope representing the rate (Lyu, S. et al,

“Kinetics and Time-Temperature Equivalence of Polymer Degradation,”Biomacromolecules, 8, 2301-11 (2007); and Kole, S. et al., “Acceleratedhydrothermal weathering of silicone-rubber, EPDMS, and their blends,” J.Applied. Polym. Sci., 54, 1329-1337 (1994)).

In order to isolate the hydrolysis reaction, oxygen should be eliminatedfrom the environment to reduce the probability of any oxidationreactions. An inert gas such as nitrogen could be used for this purpose,for example bubbling nitrogen through aqueous solutions. The pH of thetest solution should be controlled as hydrolysis reactions can becatalyzed by low or high pH, for example employing a buffered saltsolution such as PBS (Phosphate Buffered Saline) with pH 7.4 (body pH).In order to permit experiments to be performed over a relatively shorttime frame and facilitate extrapolation of results exceeding the testduration, multiple elevated temperatures should be considered includingthe use condition temperature, for example, 37° C. The use of multipletemperatures including the use condition temperature would ensure thatalternative degradation pathways are not occurring within thetemperature range of the experiments via an Arrhenius analysis. Thehydrolysis reaction could be monitored at various time points for eachtemperature and a 37° C. master curve established using time-temperatureequivalence, the slope of which would give the hydrolysis rate and allowextrapolation to longer time periods.

At the various time points, samples are taken to determine molecularweight via SEC (Size Exclusion Chromatography). Further sample formatscould be selected that would permit suitable evaluation of otherpertinent parameters including mechanical properties (for exampletensile properties).

A 37° C. master curve showing the hydrolysis kinetics of ReferencePolymer X is depicted in FIG. 6 via a reciprocal number averagemolecular weight plot with the rate constant given by the slope of thestraight line.

Example 1

This example demonstrates a hydrolysis mechanism and its generalcatalysis for both a commercially available silicone polyurethanepolymer and the PDMS diol precursor used in its preparation, with theformation and identification of lower molecular weight silanolhydrolysis products not present in the starting materials via GC-MS andNMR techniques. For example, after subjecting the silicone polyurethaneand the PDMS diol precursor to elevated temperature in deionized (DI)water or phosphate buffered saline (PBS) buffer (up to 85° C., 1-6weeks), GC-MS of the aqueous phase showed the presence of water-solublehydrolysis products consisting of small oligomer unitsdimethylsilanediol (MDM) and tetramethyldisilanediol (MD₂M). Theseproducts were further confirmed by GC-MS after trimethylsilylationderivatization of the hydroxyl groups using BSTFA. Derivatization andGC-MS of the PDMS phase for the PDMS diol hydrolysis reaction showed thepresence of non-water soluble hydrolysis products includinghexamethyltrisilanediol (MD₃M), octamethyltetrasilanediol (MD₄M) andhigher PDMS oligomer hydrolysis products.

Further, the PDMS hydrolysis reaction could be catalyzed by acid orbase. Briefly, one hundred (100) μL of PDMS (molecular weight 1000 Da,dimethyl or alkyl ether diol terminated) were mixed with 1.3 mL oftetrahydrofuran, and 100 μL of NaOH solution (50 mM) was added tohydrolyze the polymer. The homogenous reaction mixture was placed intoan NMR tube at room temperature. ²⁹Si-NMR spectra were recorded atdifferent time points. Over time, new peaks corresponding to thehydrolyzed products were observed. Peaks from −19 ppm to −21 ppmcorresponded to Si in the main chain PDMS, and their intensity were usedto indicate the hydrolysis rate. In a similar experiment, H₂SO₄ (100 mM)was also used to replace the NaOH solution for the acid-catalyzedhydrolysis experiment. In both experiments, the silicone NMR signaldecreased from the PDMS main chain, indicating the progressivehydrolysis reaction. The hydrolyzed polymers were further analyzed byGC-MS after trimethylsilylation of the hydroxyl groups using BSTFA(N,O-bis(trimethylsilyl)trifluoroacetamide) and TMCS(trimethylchlorosilane). The GC-MS chromatograms clearly showed that thePDMS was hydrolyzed into small oligomer units such as dimethylsilanediol(MDM), tetramethyldisilanediol (MD₂M), and octamethyltetrasiloxane (D₄).

Further hydrolysis studies were conducted on a model compound thatcontained the unique ether and urethane linkages and the siloxane bondsintroduced in the silicone-urethane copolymers. The chemical structureof the PDMS-polyurethane model compound is shown below.

To synthesize the model compound, the PDMS diol utilized in thesilicone-polyurethanes was reacted with 4-methylphenyl isocyanate.Bis(hydroxyethoxypropyl)polydimethylsiloxane (molecular weight˜1000 Da)(299.2 mg, 0.243 mmol) was dissolved in chloroform (1 mL) and4-methylphenyl isocyanate (76.67 μL/80.97 mg, 0.519) was added. Thereaction mixture sat undisturbed for one week. Liquid chromatography wasused to purify the reaction products. The reaction products were elutedin 20% ethyl acetate/80% hexanes. A 10 g column was run on the Biotageautomated column using these TLC measurements. The first fraction wasplaced into a 100 mL round bottom flask and evaporated to remove thesolvent. A proton NMR was conducted in CDCl₃ and showed the desiredproduct was obtained. ¹H NMR (THF-d8, 400 MHz, ppm): δ 8.66 (s, 2H),7.33 (d, J=8.5 Hz, 4H), 7.00 (d, J=8.4 Hz, 4H),4.17(t, J=4.8 Hz, 4H),3.56 (overlay, 4H), 3.39 (t, J=6.6 Hz, 4H), 2.23 (s, 6H), 1.59 (p, J=7.5Hz, 4H), 0.58 (m, 4H), −0.09-0.24(m, 77H).

The hydrolysis study was conducted by dissolving the model PDMS urethanecompound (64 mg) in a miscible solution comprised of 3.2 mL THF-d8 and0.25 mL PBS (pH 7.4). The solution was stored at 60° C. to increase thereaction kinetics. NMR spectra were acquired at room temperature tomonitor the reaction. After 8 weeks at 60° C., the peak in the ¹H NMRspectrum corresponding to the methylene next to the first siloxaneshifted and new PDMS peaks were observed (FIG. 7). After 9 weeks at 60°C., a new peak was observed in the ²⁹Si spectrum at −14.2 ppm,corresponding to Si(CH₃)₂—OH (FIG. 8).

All these results lead to the conclusion that the major degradationmechanism in silicone-polyurethane is siloxane hydrolysis.

Example 2 Synthesis of Silicone-Polyurethane Using PDMS Diol withMolecular Weight Equal to or Higher than 1000 Da

Silicone polyurethane synthesized with longer PDMS chains showed slowerdegradation due to hydrolysis. FIG. 9 shows that the polyurethane madewith short chain PDMS (repeat unit n=2) was hydrolyzed at a much fasterrate than polyurethane made with longer PDMS (repeat unit n=10-11,molecular weight approximately 1000 Da).

Using PDMS with molecular weight higher than PDMS molecular weightapproximately 1000 Da (n=10-11 repeat units) to synthesize polyurethaneresults in increased hydrolytic stability.

Synthesis of PDMS Diol with High Molecular Weight

Hydride-terminated PDMS is purchased from Gelest (Product number:DMS-H21) or synthesized by the acid catalyzed ring-openingpolymerization (Polym. Mat. Sci. Eng. 1984, 50, 518). These PDMS shouldhave a molecular weight ranging from 1000 to 100,000 Da. Thehydride-terminated PDMS is then reacted with, for example, allyloxyethanol (Aldrich). Briefly, to a 3-neck round-bottom flask,hydride-terminated PDMS is added under nitrogen. The alkoxy ethanol isthen added dropwise through an addition funnel with Karstedt's catalyst.The reaction is kept at 70-80° C. for another hour. The catalyst isremoved from the polymer by charcoal treatment and further purified.

The PDMS diol structure:

wherein 10<n<1500.Synthesis of Polyurethane Using PDMS Diol with Molecular Weight Equal orHigher than 1000 Da.

Polyurethane can be synthesized by a two-step method or one-step method.The following is an example of procedure for the one-step bulkpolymerization.

A mixture of dried PDMS diol and 1,4-butanediol (BDO) is charged into apolypropylene beaker and degassed under vacuum at 80° C. After thecatalyst (dibutyltin dilaurate) is added in at 70° C. under nitrogenatmosphere, dried MDI is quickly added with rapid stirring. The viscousmixture is poured into a TEFLON beaker and cured under nitrogen at 100°C. overnight. Polyurethane is obtained after the temperature is cooledto room temperature. There are other ways to make this. One strategy isto include all the MDI first, then add the PDMS, and then the BDO.Alternatively, a two-step method can be used. For example, dried MDI ischarged to a round-bottomed flask, melted and heated to 70° C. withagitation under a nitrogen atmosphere. Dried PDMS diol is added dropwiseand the reaction allowed to proceed for a further hour prior totransferring to a TEFLON beaker. Subsequently, 1,4-butanediol is addedrapidly with or without catalyst (dibutyltin dilaurate or stannousoctoate) accompanied by vigorous stirring. The mixture is heated at 100°C. overnight to complete the reaction before cooling to roomtemperature.

Example 3 Polysiloxane with Alternative Side Groups

Another approach to slow down the hydrolysis of the siloxane bond insilicone polyurethane is to synthesize polyurethane with polysiloxaneother than PDMS. Examples will be some polysiloxane homopolymers such aspolydiethylsiloxane, polypropylsiloxane, polydibutylsiloxane, etc., andcopolymers of these species. These polysiloxane contain bulky sidegroups and could provide the steric hindrance to retard or stop thehydrolysis reaction. Some structures are shown below:

Homopolymer Examples

Copolymer Examples

These polymers can be synthesized by acid catalyzed ring-openingpolymerization of the corresponding cyclic monomers to make the hydridefunctional polymers, followed by hydrosilylation as described before. Inthe above homopolymer and copolymer exemplary structures, typical valuesof n are from 10 to 1500, typical values of m are from 1 to1000, and Ris a divalent ether-containing chain or an alkyl chain.

Examples 4 and 5 Synthesis of Silicone-Polyurethane with IncreasedHydrophobicity

Another approach to slow down the hydrolysis of silicone-polyurethane isto increase the overall hydrophobicity of the polyurethane.Specifically, to reduce the local water concentration near the PDMSmoity. Following are two approaches employed to increase thehydrophobicity of soft segment domain.

Example 4A Introducing Hydrophobic Moieties into Polyurethane at PDMSChain Ends to Slow Down Hydrolysis

In addition to introducing hydrophobic moieties into the siliconepolyurethane via the PDMS chain ends to slow hydrolysis, the examplegiven below further substitutes the alkyl ether functionality in thePDMS utilized in commercial silicone polyurethanes that couldparticipate in facilitating/catalyzing siloxane hydrolysis.

PDMS diol used in commercially available silicone polyurethanestypically have the structure:

Further, by increasing the alkyl chain length (m) in the structure belowcould decrease the proximity of the neighboring urethane functionalityfrom the siloxane ether bonds, as this functionality may alsoparticipate in facilitating siloxane ether hydrolysis.

The modified PDMS structure:

wherein n is from 10 to 1500 and m is from 0 to 18.

Two model polyurethane-PDMS compounds were synthesized using the diolutilized in the synthesis of silicone-polyurethane copolymers and amodified diol that replaced the ether oxygen with a methylene, such thatm=4 and n=9-10 in the structure shown above. The modified diol wassynthesized via hydrosilyation through the platinum-catalyzed reactionof H—(Si(CH₃)₂—O)₉₋₁₀—Si(CH₃)₂—H and 5-hexen-1-ol. Each diol was reactedwith 4-methylphenyl isocyanate to create the urethane linkage asdescribed in Example 1. The chemical structures of the two modelcompounds studied for siloxane hydrolysis rates are shown below.

The siloxane hydrolysis rates of the two model PDMS urethane compoundswere studied by NMR. The model compounds (64 mg) were dissolved in amiscible solution comprised of 3.2 mL THF-d8 and 0.25 mL PBS (pH 7.4).The solutions were stored at 60° C. Proton NMR spectra were acquired atroom temperature to monitor the reaction. The formation of a new PDMSpeak at −0.01 ppm was quantified by integration. The percent new PDMSpeak was calculated by dividing the integral of the new peak at −0.01ppm with the integral of all the PDMS peaks multiplied by 100. Thepercent new PDMS peak was plotted versus time in FIG. 10.

The kinetics of the hydrolysis reaction was evaluated using the firstorder rate equation. A plot of the natural log of the concentration ofreactants versus time was created and the hydrolysis rate was determinedfrom the slope of the line (FIG. 11).

The hydrolysis rate of the ether-containing model compound was 0.0183s⁻¹. The hydrolysis rate of the hexamethylene model compound was 0.009s⁻¹.

Therefore, replacing the ether-containing end group with a hydrophobichexamethylene end group reduced the rate of siloxane hydrolysis by half.

Synthesis of PDMS Diol with Hydrophobic End Groups

The intermediate hydride-terminated siloxane is purchased from Gelest(Product number: DMS-H21) or synthesized by the acid catalyzedring-opening polymerization (Polym. Mat. Sci. Eng. 1984, 50: 518). Thehydride-terminated siloxane is then reacted with a serial of unsaturatedalcohol such as: 9-decen-1-ol, 10-undecen-1-ol, or oleyl alcohol. Thesehydrophobic alcohols can be purchased from Aldrich.

Structure of the Unsaturated Alcohol

9-decen-1-ol: H₂C═CH(CH₂)₇CH₂OH

10-undecen-1-ol: H₂C═CH(CH₂)₈CH₂OH

oley alcohol: CH₃(CH₂)₇CH═CH(CH₂)₇CH₂OH

Briefly, to a 3-neck round-bottom flask, hydride-terminated siloxane isadded under nitrogen. The 9-decen-1-ol is then added dropwise through anaddition funnel with Karstedt's catalyst. The reaction is kept at 70-80°C. for another hour. The catalyst is removed from the polymer bycharcoal treatment and further purified with thin film evaporator.

Synthesis of Polyurethane Using the PDMS Diol with Hydrophobic EndGroups

Polyurethane can be synthesized by a two-step method or one-step method.The following is an example of procedure for the two-step bulkpolymerization.

Dried MDI is charged to a round-bottomed flask, melted and heated to 70°C. with agitation under a nitrogen atmosphere. Dried PDMS diol is addeddropwise and the reaction allowed to proceed for a further hour prior totransferring to a TEFLON beaker. Subsequently, 1,4-butanediol is rapidlyadded with/without catalyst (dibutyltin dilaurate or stannous octoate)accompanied by vigorous stirring. The mixture is heated at 100° C.overnight to complete the reaction before cooling to room temperature.

Example 4B Introducing Hydrophobic Moieties into Polyurethane at PDMSChain Ends to Slow Down Hydrolysis 1.1 Synthesis of PMDS-C6-Diol

Hydride terminated PDMS (51 gram, 0.045 mol) was mixed with 5-hexen-1-ol(10.4 g, 0.1 mol) in 80 ml toluene. 2.1 mL of chloroplatinic acidsolution was added and the reaction mixture was heated to refluxovernight. After cooling to RT, 100 mL of heptane was added and organiclayer was wash with water for 5 times, and then dried over magnesiumsulfate. The excess 5-hexen-1-ol was removed by distillation and 59grams of PDMS-C6-diol is obtained as clear oil (yield 95%). ¹H-NMR wasused to characterize the PDMS-C6-diol. ¹H NMR (CDCl3, 400 MHz) δ 3.62(t, 4H), 1.55 (m, 4H), 1.45 (broad, 2H), 1.33 (m, 12H), 0.52 (t, 4H),0.04 (m, 96H).

1.2 Synthesis of PHMO

PHMO was synthesized by acid catalyzed condensation method. Briefly, 100g of 1,6-hexan-diol was heated to 170° C. in the presence ofconcentrated sulfuric acid. Polymerization is monitored by 1H-NMR andstopped when targeted molecular weight is obtained. PHMO with molecularweight (Mn by NMR) of 620 was synthesized.

1.3 Synthesis of PDMS-C6-Polyurethane

PDMS-C6-diol (5 g, 3.65 mmol) synthesized was mixed with PHMO diol (1.29g, 2.08 mmol) in 50 mL of THF and 50 mL of DMF mixture. The solution washeated to 65° C. and 3.2 g of MDI was added with DBTDL as catalyst.After 1 hour, 0.63 g of 1,4-butanediol was added as chain extender. Thereaction continued 50° C. overnight. Polyurethane was obtained byprecipitating into methanol solution. Evidence the polyurethane was madewas provided by NMR and GPC data

Example 5 Introducing Hydrophobic Segment to Slow Down Hydrolysis

Another way to increase the hydrophobicity of polyurethane is to usehydrophobic co-soft segment and/or chain extender. Following are somediols that can be used as the co-soft segment/chain extender to preparepolyurethane with PDMS.

Amorphous Hydrophobic Telechelic Hydrocarbon Diols

These amorphous, hydrophobic telechelic hydrocarbon diols (wherein n isfrom 1 to 30) can be synthesized using acyclic diene metathesis (ADMET)polymerization (Benz et al., U.S. Pat. No. 7,101,956; MacromolecularChemistry and Physics, 2009, 210 (21): 1818-1833.). The hydrocarbonbackbone is based on a mimic of an ethylene/isobutylene polymer, made bythe ADMET polymerization of a gem-dimethyl substituted α,ω-dienefollowed by hydrogenation of the polymer's repeat unit unsaturation.Chain termination reactants (CTR's) having one, three, and ninemethylene “spacers,” respectively, between their olefin and alcoholprecursor group are used to cap the polymer chain ends to yield 2.0functional telechelics. Use of the medium length CTR in apolymerization-depolymerization scheme, results in amorphous (Tg=−56°C.) telechelic diols with good molecular weight control.

PIB-Diol

The structure of PIB diol is shown below (wherein n is from 5 to 50),and it can be prepared by cationic polymerization of isobutylene andfurther chain-end modification, which is described in the method ofInternational Pub. No. WO 2008/066914.

Aliphatic Diols

Aliphatic diols made from natural products, such as C19-diol and dimerdiol, have been prepared and used in the industry with large scale.C19-diol can be synthesized from oleyl alcohol by hydroformylation andreduction (U.S. Pat. No. 4,243,818). Dimer diol (C36-diol, whereinx+y=33 and m+n=33) can be synthesized by dimerization of fatty acid andfollowed by hydrogenation. This type of diol also offers hydrophobicityand can be used with PDMS as a soft segment and/or chain extender tosynthesize polyurethane.

Fluorinated Telechelic Diol

A fluorinated telechelic diol with structure shown below can besynthesized according to the literature (Journal of Fluorine chemistry,2001(107): 81-88). It can be used to synthesize polyurethane with PDMSto increase the hydrophobicity as a co-soft segment or chain extender.

HOC₃H₆—C₆F₁₂—C₃H₆OH

Disilane Diol

A silane diol with structure shown below can be prepared according toBenz's method (U.S. Pat. Pub. No. 2004/0054113). And it also can be usedto prepare polyurethane with PDMS.

Example of Procedure for the One-Step Bulk Polymerization.

Polyurethane can be synthesized by a two-step method or one-step method,and following is an example of procedure for the one-step bulkpolymerization.

A mixture of dried PDMS diol, PIB diol, and 1,4-butanediol is chargedinto a polypropylene beaker and degassed under vacuum at 80° C. Afterthe catalyst (dibutyltin dilaurate) is added in at 70° C. under nitrogenatmosphere, dried HMDI is quickly added with rapid stirring. The viscousmixture is poured into a Teflon beaker and cured under nitrogen at 100°C. overnight. Polyurethane is obtained after the temperature is cooledto room temperature.

The hydrophobicity of the hard segment in silicone-polyurethane can alsobe increased by replacing the conventional chain extender 1,4-butandiolwith 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol,1,10-decanediol, and the hydrophobic diols described above.

Example 6 Biostable Silicone Polyurethane with Crosslinked Soft Segment

Crosslinked materials are mechanically stable due to their networkedstructure. For example, silicone adhesive/sealant is mechanically stablefor a long period time even in contact with water. In an analogousmanner to this phenomenon, silicone-polyurethane with crosslinkedpolysiloxane moiety should have longer mechanical stability than thatwithout crosslinking.

One approach to crosslink PDMS is to use radical reaction, similar tothe crosslinking method used in the silicone tubing. Since thepolyurethane tubing is extruded at high temperature, a radical generatorsuch as dicumyl peroxide, Di-t-amyl peroxide, and Di-t-butyl peroxidewill be used to crosslink the PDMS domain in the polyurethane. Duringthe extrusion, a small percentage of the peroxide is introduced into thepolyurethane and mixed in the extruder. These peroxides decompose athigh temperature and have reasonable half-lives at 150-160° C. Thisallows the PDMS domain to be crosslinked while the polyurethane is beingextruded. Post-extrusion cure is possible if necessary. Other radicalgenerator could be used if those mentioned above do not give desiredcrosslink density.

Alternatively, a vinylmethylsiloxane-dimethylsiloxane copolymer(structure shown below) can be introduced to facilitate the crosslink.These copolymers can be purchased from Gelest (product number: VDT-123to VDT-954). A small percentage (5-10%) of the copolymer is blended withsilicone-polyurethane during the extrusion, and the copolymer will gointo the PDMS domain due to the phase separation. At high temperature,the soft segment containing the PDMS andvinylmethylsiloxane-dimethylsiloxane copolymer (structure shown belowwherein m is from 1 to 100 and n is from 2 to 10) can be crosslinkedwith or without need of a radical initiator.

Another approach to crosslink the PDMS in the urethane is to prepare thesilicone-polyurethane with polysiloxane copolymer containingcrosslinkable units. These crosslinkable units will only react with eachother at high temperature. For example, a copolymer of PDMS withmultiple pendent benzocyclobutene (BCB) groups is used as a soft segmentfor making polyurethane. Due to the strained four-member ring, the BCBcan be converted to o-xylylene at temperatures above 180° C., and reactwith itself to form an 8-member ring. This allows us to thermallyprocess the polyurethane by extrusion or compression molding withoutpremature cure. The crosslinked PDMS domain will maintain the mechanicalproperties longer than the non-crosslinked version upon the same degreeof degradation (mainly hydrolysis). Additionally, the hydrophobic BCBgroup will decrease the water absorption in the polyurethane, which inturn slows down the hydrolysis reaction.

By controlling the content of BCB in the polysiloxane oligiomer, thecrosslinking density can be controlled.

wherein m is from 2 to 10 and n is from 10 to 1500.

The complete disclosures of the patents, patent documents, andpublications cited herein are incorporated by reference in theirentirety as if each were individually incorporated. Variousmodifications and alterations to this disclosure will become apparent tothose skilled in the art without departing from the scope and spirit ofthis disclosure. It should be understood that this disclosure is notintended to be unduly limited by the illustrative embodiments andexamples set forth herein and that such examples and embodiments arepresented by way of example only with the scope of the disclosureintended to be limited only by the claims set forth herein as follows.

1. A medical lead comprising an elongated lead body comprising apolymeric material, wherein the polymeric material comprises asilicone-urethane polymer having hydrolytic stability greater than thatof a Reference Polymer X, a Reference Polymer Y, or both ReferencePolymers X and Y. 2-33. (canceled)